{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:37:51Z","timestamp":1793039871746,"version":"4.5.0"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Metabolic and neurovascular disturbances contribute to brain injury after birth asphyxia. We previously showed that plasma feeding attenuated neuropathology after transient umbilical cord occlusion in piglets. This study explored the metabolic and molecular consequences of birth asphyxia and whether plasma feeding preserves metabolic homeostasis and brain barrier integrity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Piglets (n=89) delivered by cesarean section on gestational day 113 underwent umbilical cord occlusion (asphyxia [ASP]) or remained nonasphyxiated (control [CON]). ASP and CON piglets were randomly assigned to receive formula reconstituted with either water (vehicle-treated group) or sow plasma (plasma-treated group). Animals were euthanized at 1 hour, 24 hours, or day 4 after insult. Cerebrospinal fluid metabolites were profiled by untargeted liquid chromatography\u2013mass spectrometry metabolomics at 24 hours. Expression of metabolite transporters and structural components of the blood-brain barrier in the caudate nucleus and the blood\u2013cerebrospinal fluid barrier at the choroid plexus was assessed by reverse transcription quantitative polymerase chain reaction and Western blotting. The CSF\/plasma Na\n                      <jats:sup>+<\/jats:sup>\n                      ratio was assessed, and cell-specific\n                      <jats:italic toggle=\"yes\">AQP4<\/jats:italic>\n                      expression was confirmed with RNAscope. Data were analyzed using linear and linear mixed-effects models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Birth asphyxia dysregulated the CSF metabolic profile, with reductions in multiple metabolites and increases in a smaller subset, consistent with impaired amino acid and lipid metabolism. This was accompanied by reduced expression of substrate transporters, including\n                      <jats:italic toggle=\"yes\">xCT<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">LAT1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">ASCT2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">FATP1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">CAV1<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">MCTs<\/jats:italic>\n                      . In the caudate nucleus, expression of blood-brain barrier structural proteins and ion transporters, including Na\n                      <jats:sup>+<\/jats:sup>\n                      \/K\n                      <jats:sup>+<\/jats:sup>\n                      -ATPase, was reduced, whereas the choroid plexus blood-CSF barrier remained largely preserved. Plasma feeding partially restored transporter expression at both brain interfaces and increased\n                      <jats:italic toggle=\"yes\">AQP4<\/jats:italic>\n                      and ion transporter expression at the blood-brain barrier by day 4. Increased VE-cadherin (vascular endothelial cadherin) and ZO-1 (zonula occludens-1) expression and elevated CSF Na\n                      <jats:sup>+<\/jats:sup>\n                      concentrations suggested early modulation of the integrity of the 2 brain barriers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Plasma feeding preserves metabolic homeostasis and supports brain barrier integrity after birth asphyxia, highlighting plasma-derived factors as potential therapeutic targets to reduce neurodevelopmental impairment after perinatal asphyxia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.126.056579","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:00:15Z","timestamp":1789635615000},"page":"3418-3430","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma Feeding Protects the Blood-Brain Barrier Post-Asphyxia While the Blood-CSF Barrier Remains Spared"],"prefix":"10.1161","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4396-797X","authenticated-orcid":true,"given":"Gemma Chavarria","family":"Ventura","sequence":"first","affiliation":[{"name":"Comparative Pediatrics, Section for Biomedicine, Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark (G.C.V., L.I.C., T.T., P.T.S., P.-P.J., S.P.)."},{"name":"Fazer Institute, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, Australia (G.C.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0339-0302","authenticated-orcid":true,"given":"Line Iadsatian","family":"Christiansen","sequence":"additional","affiliation":[{"name":"Comparative Pediatrics, Section for Biomedicine, Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark (G.C.V., L.I.C., T.T., P.T.S., P.-P.J., S.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2075-338X","authenticated-orcid":true,"given":"Oksana","family":"Dmytriyeva","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research (O.D.), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3801-1165","authenticated-orcid":true,"given":"Viktor Karlovich","family":"Lund","sequence":"additional","affiliation":[{"name":"Department of Neuroscience (V.K.L., S.P.), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7480-6064","authenticated-orcid":true,"given":"Thomas","family":"Thymann","sequence":"additional","affiliation":[{"name":"Comparative Pediatrics, Section for Biomedicine, Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark (G.C.V., L.I.C., T.T., P.T.S., P.-P.J., S.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5462-7760","authenticated-orcid":true,"given":"Per Torp","family":"Sangild","sequence":"additional","affiliation":[{"name":"Comparative Pediatrics, Section for Biomedicine, Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark (G.C.V., L.I.C., T.T., P.T.S., P.-P.J., S.P.)."},{"name":"Centre for Science and Faith, Faculty of Theology, University of Copenhagen, Denmark (P.T.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7393-9719","authenticated-orcid":true,"given":"Ping-Ping","family":"Jiang","sequence":"additional","affiliation":[{"name":"Comparative Pediatrics, Section for Biomedicine, Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark (G.C.V., L.I.C., T.T., P.T.S., P.-P.J., S.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5406-5163","authenticated-orcid":true,"given":"Stanislava","family":"Pankratova","sequence":"additional","affiliation":[{"name":"Comparative Pediatrics, Section for Biomedicine, Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark (G.C.V., L.I.C., T.T., P.T.S., P.-P.J., S.P.)."},{"name":"Department of Neuroscience (V.K.L., S.P.), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","volume-title":"Basic Neurochemistry: Molecular, Cellular, and Medical Aspects","author":"Siegel GJ","year":"1999","unstructured":"Siegel GJ. Basic Neurochemistry: Molecular, Cellular, and Medical Aspects. 6th ed. Lippincott Williams & Wilkins; 1999","edition":"6"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1323099111"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.11.020"},{"key":"e_1_3_3_5_2","volume-title":"Hypoxic Brain Injury","author":"Lacerte M","year":"2025","unstructured":"Lacerte M, Shapshak AH, Mesfin FB. Hypoxic Brain Injury. StatPearls Publishing; 2025"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3474"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a020412"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/pnasnexus\/pgae496"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00041.2017"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST20220830"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1017\/s0317167100000421"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2012.05.008"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2022.115356"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18010055"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3407"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/metabo10040141"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1177\/1060028013511228"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1089\/bfm.2017.0122"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/apa.15168"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-025-04458-3"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2024.04.032"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.202200132"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-12-118"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay5947"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcaf201"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom13020212"},{"key":"e_1_3_3_27_2","volume-title":"Biochemistry, Fatty Acid Oxidation","author":"Talley JT","year":"2025","unstructured":"Talley JT, Mohiuddin SS. Biochemistry, Fatty Acid Oxidation. StatPearls; 2025"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74830"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00128238"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.3390\/metabo9020036"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2016.01.023"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-67542-6"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2011.04.007"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23978"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12617"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1159\/000545099"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X241241908"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-020-01051-z"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0174596"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-024-00613-w"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1159\/000069052"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.1"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0387-7604(03)00166-9"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2017.09.011"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.11.4067"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0169-328x(01)00032-8"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)90085-y"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.07.003"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.3390\/pediatric16030061"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1159\/000488979"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.32.2.553"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.07.015"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.838543"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-35799-w"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-024-03376-0"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.5409\/wjcp.v5.i1.67"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.126.056579","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:01:41Z","timestamp":1793037701000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.126.056579"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,11]]},"references-count":55,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1161\/STROKEAHA.126.056579"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.126.056579","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,11]]},"assertion":[{"value":"2026-04-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-19","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}